The Hong Kong Science Museum began as an idea inside the Urban Council in 1976, long before the land in Tsim Sha Tsui East had been reclaimed from the harbour. The council hired American planning firm E. Verner Johnson and Associates in 1984 to help shape the concept. Two years later it brought in Hong Kong architecture firm Palmer and Turner to design the building. Construction by Leighton Contractors began in March 1988 and completed in November 1990. The museum opened the following year in April 1991, one of a cluster of cultural institutions being built along the Kowloon waterfront as Hong Kong invested in its identity as an international city. Next door, the Hong Kong Museum of History would follow.

The permanent exhibition spans 18 galleries covering light, sound, motion, electricity and magnetism, mathematics, life science, geography, meteorology, transportation, communication, and more. About 500 exhibits fill the permanent area, and roughly 70 percent of them are participatory. Children can sit in a real stationary car and take a driving simulation that tests their ability to avoid accidents and manage fuel use. They can step inside a life-sized aircraft cockpit and watch footage of a flight over Hong Kong play on the screen in front of them. Museum staff perform live demonstrations daily. The emphasis on doing rather than reading reflects a particular philosophy: that the most durable way to understand a principle is to feel it work.

In 2016, the Biodiversity Gallery opened on the ground floor, exploring the flora and fauna of different habitats, with a focus on Hong Kong's own ecological variety. Visitors can explore genetics, evolution, and microscopy at its hands-on stations. The Paleontology Gallery, which opened in 2023 under the name Extinction · Resilience, houses 80 to 100 fossils and replicas, anchored by an almost complete Deinonychus skeleton. Two dinosaur animatronics — a Tyrannosaurus rex and a Velociraptor — respond to visitors. The Jockey Club Environmental Conservation Gallery tackles climate change through games and interactive displays. The museum evolves: as of 2025 the second floor is under renovation as part of a broader permanent exhibition renewal project.

In late 2023, the Hong Kong government proposed relocating the Science Museum to Sha Tin, freeing the Tsim Sha Tsui site for a new institution that would, according to the proposal, showcase Chinese history, the Communist Party, and national achievements. The Culture, Sports and Tourism Bureau framed it as an opportunity to improve teenagers' understanding of China. The proposal generated strong public opposition, and by 2024 the government had quietly shelved the relocation — exploring alternative sites for the new national museum instead. The Science Museum stayed. The DC-3 still hangs from the ceiling in Tsim Sha Tsui. The Energy Machine still runs.